Cancer cells produce energy in a different way - could this be their Achilles' heel?

Scientists have been researching cell metabolism – how our cells produce and use energy – for decades. And this is a particularly pertinent topic in cancer, as cancer cells seem to use energy differently from normal cells.

In recent years there has been a renewed interest in the area. And at this year’s NCRI Cancer Conference, the crowded lecture hall illustrated this recent surge in excitement.

Setting the scene

In order to survive, our cells have to produce energy – but on a tiny scale. They need this energy to carry out all their daily activities like growth and repair. And they use a complicated series of chemical reactions to produce energy from oxygen.

But the conditions in which cancer cells grow are unique. They multiply much faster then normal cells and have much higher energy demands. Cancer cells learn to change and adapt their metabolism to their surroundings. They learn to produce energy without oxygen in a process called anaerobic metabolism.

Professor Peter Ratcliffe from the University of Oxford chaired the session, beginning with a history lesson stretching back nearly 70 years.

The study of cancer metabolism started in the 1940s, when a scientist called Otto Warburg noted that rapidly dividing cancer cells didn’t consume oxygen in the same way as rapidly dividing normal cells.

Warburg noted that, even when oxygen was in plentiful supply, cancer cells still produced their energy using ‘oxygen-less’ anaerobic metabolism. This led him to believe that this change was no mere byproduct of cancer – it was the fundamental cause of cancer.

But his work didn’t really capture the imagination of the global cancer research community – partly because of the discovery of DNA and the genetic basis of cancer. And so progress in this field faltered.

However, more recent investigations have shown that Warburg’s early observations could be key to helping us target and treat cancer cells. Although we know that cancer is caused by faults in key genes, the speakers at the session did an excellent job of showing that metabolism still plays a very important role.

Genes and metabolism

Cancer Research UK’s Professor Ian Tomlinson, from the University of Oxford, focused on some of the genetic changes that can affect metabolism. He and his team have been investigating rare types of cancer where faults in genes which control metabolism appear to play a key role in cancer development.

This is helping him understand more about how metabolism is linked to cancer development in general. But the big challenge is to show that these genetic links hold true for more common cancers, as well as the rarer ones.

Here’s a short interview with Professor Tomlinson (3min 24s), explaining more about his research:

Several of the speakers focused on how cancer cells cope with a condition called hypoxia – which occurs when cells lack oxygen. Hypoxia triggers important changes in the cell, switching on certain genes which are normally turned off, including a gene called HIF1.

HIF1, which was the focus of several talks, is turned on in hypoxic conditions and, in effect, gives cancer cells ‘special powers’.

It can help them both attract new blood vessels to deliver more oxygen and nutrients, and invade surrounding tissues and spread around the body. It can even help cells develop drug resistance. And these are all hallmarks of cancer.
Future treatments

One of the session’s highlights was Professor Gregg Semenza form the John Hopkins University school of Medicine in the US, who has been searching for chemicals that block HIF1, which could be useful for future cancer drugs.

He has focused on testing drugs which have already been approved by the FDA or those which have already been through early clinical trials in people and have been shown to be safe.

Professor Semenza hopes this will speed up the discovery of new treatments and get them quickly to people with cancer. He has isolated 23 chemicals that block HIF1, and is now investigating which of these is most suitable to be taken forward for further tests.

There’s a lot of work still to do but Professor Semenza closed his talk by saying that targeting the unusual metabolism of cancer cells could be a real opportunity for developing new treatments.

So understanding cell metabolism looks like it could play an important part in beating cancer. Recent work in the field has shown there are many connections between cancer development and changes in metabolism which potentially explain Warburg’s early observations.

The differences between normal and cancer cell metabolism have already allowed us to develop PET scanning – currently one of the most effective ways of diagnosing cancer. And some therapies that target tumour metabolism are already being tested in early clinical trials.

The experts at this conference seemed hopeful that drugs which target metabolism could be at the forefront of cancer treatments in coming years.

Laura Bell

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Comments

Hi Sean,
Thanks for raising an important point. The ‘oxygen therapy’ you mention involves taking drugs that are supposed to release oxygen. But as you say, available scientific evidence does not support claims that increasing oxygen levels in the body will harm or kill cancer cells.

Since Warburg’s early observations we have learned a lot about how cells produce energy from oxygen. Even if more oxygen is available, it does not cause cancer cells to switch back to normal oxygen use. And, higher oxygen levels have not been shown to damage cancer cells any more than normal cells.

The scientists who presented their work at the NCRI conference are investigating how a cancer cell’s altered metabolism affects how their genes are turned on and off.

The hope is that increasing their knowledge about the differences between cancer cells and normal cells will help them understand which genes could be targeted with therapies to specifically damage cancer cells (such as the chemicals that block HIF1 that I mentioned in the blog). This approach is quite different to ‘oxygen therapy’.

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